Vaccinia virus lacking the Bcl-2-like protein N1 induces a stronger natural killer cell response to infection.
The vaccinia virus (VACV) N1 protein is an intracellular virulence factor that has a Bcl-2-like structure and inhibits both apoptosis and signalling from the interleukin 1 receptor, leading to nuclear factor kappa B activation. Here, we investigated the immune response to intranasal infection with a virus lacking the N1L gene (vDeltaN1L) compared with control viruses expressing N1L. Data presented show that deletion of N1L did not affect the proportion of CD4+ and CD8+ T cells infiltrating the lungs or the cytotoxic T-cell activity of these cells. However, vDeltaN1L induced an increased local natural killer cell activity between days 4 and 6 post-infection. In addition, in the absence of N1 the host inflammatory infiltrate was characterized by a reduced proportion of lymphocytes bearing the early activation marker CD69. Notably, there was a good correlation between the level of CD69 expression and weight loss. The implications of these findings are discussed.
Jacobs
Nathalie
N
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Bartlett
Nathan W
NW
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Clark
Richard H
RH
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Smith
Geoffrey L
GL
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019254:Genes, bcl-2; D006801:Humans; D007239:Infections / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency* / Q000276:immunology; D012899:Smallpox / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D010948:Viral Plaque Assay
D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2